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dc.contributor.authorCoutandin, Daniel
dc.contributor.authorOsterburg, Christian
dc.contributor.authorSrivastav, Ratnesh Kumar
dc.contributor.authorSumyk, Manuela
dc.contributor.authorKehrloesser, Sebastian
dc.contributor.authorGebel, Jakob
dc.contributor.authorTuppi, Marcel
dc.contributor.authorHannewald, Jens
dc.contributor.authorSchäfer, Birgit
dc.contributor.authorSalah, Eidarus
dc.contributor.authorMathea, Sebastian
dc.contributor.authorMüller-Kuller, Uta
dc.contributor.authorDoutch, James
dc.contributor.authorGrez, Manuel
dc.contributor.authorKnapp, Stefan
dc.contributor.authorDötsch, Volker
dc.date.accessioned2018-11-14T00:30:25Z
dc.date.available2018-11-14T00:30:25Z
dc.date.issued2016-03-14
dc.identifier.issn2050-084X
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/285018
dc.description.abstractMammalian oocytes are arrested in the dictyate stage of meiotic prophase I for long periods of time, during which the high concentration of the p53 family member TAp63α sensitizes them to DNA damage-induced apoptosis. TAp63α is kept in an inactive and exclusively dimeric state but undergoes rapid phosphorylation-induced tetramerization and concomitant activation upon detection of DNA damage. Here we show that the TAp63α dimer is a kinetically trapped state. Activation follows a spring-loaded mechanism not requiring further translation of other cellular factors in oocytes and is associated with unfolding of the inhibitory structure that blocks the tetramerization interface. Using a combination of biophysical methods as well as cell and ovary culture experiments we explain how TAp63α is kept inactive in the absence of DNA damage but causes rapid oocyte elimination in response to a few DNA double strand breaks thereby acting as the key quality control factor in maternal reproduction.
dc.format.mediumElectronic
dc.languageeng
dc.publishereLife Sciences Publications, Ltd
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectOocytes
dc.subjectAnimals
dc.subjectMice
dc.subjectDNA Damage
dc.subjectTrans-Activators
dc.subjectPhosphoproteins
dc.subjectApoptosis
dc.subjectProtein Processing, Post-Translational
dc.subjectPhosphorylation
dc.subjectQuality Control
dc.subjectFemale
dc.subjectProtein Multimerization
dc.titleQuality control in oocytes by p63 is based on a spring-loaded activation mechanism on the molecular and cellular level.
dc.typeArticle
prism.publicationDate2016
prism.publicationNameElife
prism.volume5
dc.identifier.doi10.17863/CAM.32388
dcterms.dateAccepted2016-03-28
rioxxterms.versionofrecord10.7554/eLife.13909
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2016-03-14
dc.contributor.orcidKehrloesser, Sebastian [0000-0002-6791-2421]
dc.contributor.orcidDötsch, Volker [0000-0001-5720-212X]
dc.identifier.eissn2050-084X
rioxxterms.typeJournal Article/Review
cam.issuedOnline2016-03-14


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International